Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis

source extracted confidence: high 2026-04-09
#antipsychotic-agents #bipolar-disorder #humans #melatonin #metabolic-syndrome

Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis

Miola et al., 2022 | Hum Psychopharmacol | Meta Analysis

Citation

Miola Alessandro, Fornaro Michele, ... Solmi Marco. Melatonin and melatonin-agonists for metabolic syndrome components in patients treated with antipsychotics: A systematic review and meta-analysis. Hum Psychopharmacol. 2022-Mar;37(2):e2821. doi:10.1002/hup.2821

Abstract

OBJECTIVE: Metabolic side effects are a limiting factor in the use of antipsychotics, which remain the cornerstone of long-term management of patients with severe mental illness. There is contrasting evidence on a possible role of melatonin and melatonin-agonists in attenuating antipsychotic-induced metabolic abnormalities. DESIGN: We conducted a systematic review (PubMed, PsycInfo, Cochrane databases, up to August 2020) and a random-effect meta-analysis of double-blind, randomized placebo-controlled trials (RCTs) involving melatonin and melatonin-agonists in the treatment of antipsychotic-induced metabolic changes. The primary outcome was the standardized mean difference (SMD) of composite metabolic outcomes built with metabolic syndrome components. Secondary outcomes were individual metabolic syndrome components, and other anthropometric, glucose metabolism, lipid profile, and psychopathology measures. RESULTS: Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia-spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD -0.28, 95% CI = -0.39 ÷ -0.168), as well as on all individual components of metabolic syndrome (systolic blood pressure MD -3.266, 95% CI = -6.020 ÷ -0.511; fasting glucose MD -3.766, 95% CI = -5.938 ÷ -1.593; triglycerides MD -9.800, 95% CI = -19.431 ÷ -0.169; HDL MD 2.995, 95% CI = 0.567 ÷ 5.423), except waist circumference. CONCLUSIONS: Melatonin/ramelteon augmentation may be beneficial for non-anthropometric metabolic syndrome components in patients treated with antipsychotics.

Key Findings

Out of the initial 41 studies, six documented five separate RCTs randomizing 248 patients (126 to melatonin/ramelteon, 122 to placebo) affected by schizophrenia-spectrum disorders and bipolar disorder. Melatonin/ramelteon outperformed placebo on the primary outcome (SMD -0.28, 95% CI = -0.39 ÷ -0.168), as well as on all individual components of metabolic syndrome (systolic blood pressure MD -3.266, 95% CI = -6.020 ÷ -0.511; fasting glucose MD -3.766, 95% CI = -5.938 ÷ -1.593; triglycerides MD -9

Outcomes Measured

  • blood pressure
  • systolic blood pressure

Population

Field Value
Population severe mental illness
Sample Size 248
Age Range See abstract
Condition blood pressure

MeSH Terms

  • Antipsychotic Agents
  • Bipolar Disorder
  • Humans
  • Melatonin
  • Metabolic Syndrome
  • Randomized Controlled Trials as Topic
  • Schizophrenia

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: melatonin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09